Global variability of the human IgG glycome.

Immunoglobulin G (IgG) is the most abundant serum antibody which structural characteristics and effector functions are modulated through the attachment of various sugar moieties called glycans. Composition of the IgG N-glycome changes with age of an individual and in different diseases. Variability of IgG glycosylation within a population is well studied and is known to be affected by both genetic and environmental factors. However, global inter-population differences in IgG glycosylation have never been properly addressed. Here we present population-specific N-glycosylation patterns of IgG, analyzed in 5 different populations totaling 10,482 IgG glycomes, and of IgG's fragment crystallizable region (Fc), analyzed in 2,579 samples from 27 populations sampled across the world. Country of residence associated with many N-glycan features and the strongest association was with monogalactosylation where it explained 38% of variability. IgG monogalactosylation strongly correlated with the development level of a country, defined by United Nations health and socioeconomic development indicators, and with the expected lifespan. Subjects from developing countries had low levels of IgG galactosylation, characteristic for inflammation and ageing. Our results suggest that citizens of developing countries may be exposed to environmental factors that can cause low-grade chronic inflammation and the apparent increase in biological age.

Citation

Jerko Štambuk, Natali Nakić, Frano Vučković, Maja Pučić-Baković, Genadij Razdorov, Irena Trbojević-Akmačić, Mislav Novokmet, Toma Keser, Marija Vilaj, Tamara Štambuk, Ivan Gudelj, Mirna Šimurina, Manshu Song, Hao Wang, Marijana Peričić Salihović, Harry Campbell, Igor Rudan, Ivana Kolčić, Leigh Anne Eller, Paul McKeigue, Merlin L Robb, Jonas Halfvarson, Metin Kurtoglu, Vito Annese, Tatjana Škarić-Jurić, Mariam Molokhia, Ozren Polašek, Caroline Hayward, Hannah Kibuuka, Kujtim Thaqi, Dragan Primorac, Christian Gieger, Sorachai Nitayaphan, Tim Spector, Youxin Wang, Therese Tillin, Nish Chaturvedi, James F Wilson, Moses Schanfield, Maxim Filipenko, Wei Wang, Gordan Lauc. Global variability of the human IgG glycome. Aging. 2020 Aug 12;12(15):15222-15259

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PMID: 32788422

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